JPS6097986A - Production of organophosphoric acid ester derivative - Google Patents

Abstract

PURPOSE:To produce the titled compound useful as an insecticidal and miticidal agent, in high yield and purity, by reacting an organophosphoric acid ester halide with an OH-containing compound in water and water-immiscible solvent under basic condition. CONSTITUTION:The objective compound of formula II can be produced by reacting the compound of formula I (R1 is lower alkoxy; R2 is lower alkoxy or lower alkylthio; X is O or S; Y is halogen) with the compound of formula R3OH (R3 is substitutable phenyl or substitutable heterocyclic group) in water and a solvent which cannot be mixed homogeneously with water, under basic condition. The compound of formula I is e.g. O,O-dimethyl-O-(4-cyanophenyl)-phosphorothioate, etc. The amount of the compound of formula I is about 0.5-3mol per 1mol of the compound of formula R3OH. The water-immiscible solvent is e.g. benzene, toluene, xylene, etc.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for producing an organic phosphate derivative having insecticidal, acaricidal, and bactericidal activity and useful as an agrochemical. More specifically, it is represented by the general formula [wherein R1 represents a lower alkoxy group, R8 represents a lower alkoxy group or a lower a-ki-thio group, X represents an oxygen atom or a sulfur atom, and Y represents a halogen atom]. and a compound represented by the general formula % (in the formula, R3 represents an optionally substituted phenyl group or an optionally substituted heterocyclic group) are uniformly mixed with water and water. The present invention relates to a method for producing a compound represented by the general formula [wherein R1, R2, R3 and

It is widely known that organic phosphoric acid ester derivatives are produced by reacting organic phosphoric acid ester μ halide with a compound having a hydroxyl group such as alcohol or phenol and esterifying it (for example, in 55
-83796. USP4163052 etc.). In this esterification reaction, since the organic phosphoric acid ester halide as a raw material compound is extremely easily decomposed by water, the use of water is discouraged, and the reaction is usually carried out using an organic solvent. For example, in JP-A-55-83796, 4-hydroxybilacy μ derivatives,! : O-x+μm5-n-propyl-(di)-thiophosphoric acid diester halide,
Organic solution V#, inert to the reaction (e.g. acetonitrile)
A method for producing the corresponding organophosphoric acid NTE/L' conductor is described. However, these methods are not satisfactory as industrial production methods because the yield and purity of the target compound are low, and since the reaction is carried out in an organic solvent, the operations are complicated.

The present inventors further discovered that the target compound (
As we continued our research on the method for producing I), we discovered that compound (II) and compound (II) unexpectedly reacted under basic conditions in water and a solvent that is not homogeneously miscible with water, resulting in a high yield. It was discovered that the target compound (I) could be produced at a high purity and at a high purity, and as a result of further various studies, the present invention was completed.

According to the method of the present invention, organophosphoric acid ester μ hafide, that is, compound (III), is extremely unstable in water and therefore, contrary to the conventional chemical common sense that water is inappropriate as a reaction solvent, it is possible to obtain Compound (I) can be produced in a surprisingly high yield and with high purity under basic conditions using a mixed solvent system in which water and a solvent that are immiscible form two layers.

In the above general formula, R1 is, for example, methoxy.

A linear or branched lower alkoxy group having 1 to 4 carbon atoms such as ethoxy, n-propoxy, isopropoxy, n-gutoxy, isobutoxy, tert-butoxy, etc. R2 is, for example, methoxy, ethoxy, propoxy, isopropoxy, n- Straight-chain or branched lower alkoxy groups having 1 to 4 carbon atoms such as butoxy, isobutoxy, tert-butoxy, or for example butylthio, ethylthio, n-propylthio.

Isopropylthio, n-butylthio, isobutylthio,
R3 is (1) (a
(b) halogen, (C) lower alkylthio group having 1 to 4 carbon atoms, or/and (d) cya,
a phenyl group which may be substituted with 3 to 3, or (
2) (a) Lower alkyl group having 1 to 4 carbon atoms.

A lower akoki V group having 1 to 4 carbon atoms, a lower alkylthio group having 1 to 4 carbon atoms, a phenyl group which may have 1 to 3 nitro, halogen or/and trifluoromethyμ, (b) A lower alkoxycarbonyl μ group having 1 to 4 carbon atoms, (Q) an oxo group or/and (d) optionally substituted with 1 to 3 halogens, bonded through an elemental atom;
A 5- to 6-membered heterocyclic group containing 1 to 4 nitrogen atoms, X is an oxygen atom or a sulfur atom, and Y is, for example, fluorine or chlorine.

Indicates halogens such as bromine and iodine, respectively.

In R3 above, the halogen is, for example, fluorine,
Chlorine, bromine, iodine, etc. are lower alkylthio groups having 1 to 4 carbon atoms; Examples of the alkoxy group include those defined for R2, and examples of the lower alkyl group having 1 to 4 carbon atoms include methyl, ethyl, and n-propylene.
, isopropyl A/, n-butiμ, isobuti! , tar
A linear or branched lower alkyl μ group having 1 to 4 carbon atoms such as t-butyl is used.

Examples of the 5- to 6-membered heterocyclic group containing 4 nitrogen atoms from 1 in R3 include pylori μ, viridi μ
a saturated or unsaturated 5- to 6-membered heterocyclic group containing one nitrogen atom, such as , virolidium μ, viloridine μ, piperidine μ, imidazolyl.

Pyrazolyl, pyrazinyl, pyrimidinyl, viridazinyl p
, imidazonyl, imidazolini μ, pyrazolidinyl, papiozolini IL/, biverazini y, etc., a saturated or unsaturated 5- to 6-membered heterocyclic group containing two nitrogen atoms,
A saturated or unsaturated 5- to 6-membered heterocyclic group containing 3 to 4 nitrogen atoms, such as triazolyl and tetrazolyl, is used.

Among the above, R1 is preferably a lower alkoxy group, R2
is a lower a-μ-thio group, X is an oxygen atom, and R3 has 1 carbon number.
to 4 lower alkyl μ groups, lower alkoxy groups having 1 to 4 carbon atoms, lower alkylthio groups having 1 to 4 carbon atoms, phenyl groups optionally having nitro, halogen or/and trifluoromethi μ is a saturated or unsaturated 5- to 6-membered heterocyclic group containing two nitrogen atoms, which may have two nitrogen atoms.

Among the optionally substituted heterocyclic groups represented by R3,
Particularly preferred is an unsaturated 5-membered heterocyclic group containing two nitrogen atoms, which may be substituted with a halogen-containing phenyl group.

More specific examples of the compound represented by the general formula (I) are as follows.

0.0-dimethy/L/-0-(4-5/7/7c=A/
) Phosphorothioate o,o-diethyl/l/-0-(2,4-dichlorophenylene/L/)phosphorothioate 0.0-diethy/L/-0-(5-phenylic)V-3-isoxacylyl) Phosphorothioate o,o-diethyl/l/-0-(3,5,6-dolichloro-2-pyridi/L/)phosphorothioate o-ethyl A/
-8-n-propy/L/-0-(1-(4-chlorophenylene/L/)-4-hyozoliμ)phosphorothioate 0.0-diethyl #-0-(2-isopropyl-4-methylpyrimidine-6 -i, A/) Phosphorothioate 0.0-dimethyl-〇-(4-methylthio-m-tri/l/) Phosphorithioate 0-3,5,6-)dichloro-2-pyridi/L/-
0,0-dimethymu honuholothioate 0.0-diethy/l/-0-(2,3-dihydro-3-
Oxo-2-phenyA/-6-pyridazinyl) phosphorothioate (4-methyμthiophene 1L/) di-n-propyl phosphate.

When producing the object compound (I) of the present invention, the compound (M
E) is present in an amount of about 0.5 to 3 times the mole of compound (IF), preferably about 1 to 1.055 times by mole.

In this reaction, examples of solvents used that do not mix uniformly with water include benzene, )/l/ene.

Aromatic hydrogen chloride such as xylene, methylene chloride.

Examples include halogenated hydrocarbons such as chloroform and sulfate. Among these, aromatic hydrogenated compounds such as benzene, toluene, and xylene are preferred.

In the reaction, the pull of the reaction solution ranged from 7.1 to 14.0. Preferably, the process is carried out smoothly in a basic range with a pH value of 10 to 11.

In order to carry out the reaction under basic conditions, a base is added to the compound (I[
) is used in an amount equivalent to about 0.75 mo.

Suitable bases include, for example, alkali metal hydroxides such as potassium hydroxide and sodium hydroxide, alkaline earth metal hydroxides such as calcium hydroxide, alkali metal carbonates such as potassium carbonate and sodium carbonate, potassium hydrogen, and carbonic acid. Inorganic bases such as alkali metal hydrogen carbonate such as sodium hydrogen carbonate and alkaline earth metal carbonate such as p-sium carbonate are used.

Among the above, alkali metal hydroxides such as potassium hydroxide and sodium hydroxide are particularly preferred.

The reaction usually proceeds in two layers: an aqueous layer and a solvent layer that is not homogeneously mixed with water. In the reaction, compound (II) is added to water and a solvent that is not homogeneously mixed with water, and then compound (I[)
The reaction may also be carried out while adding a base to maintain the pH value of the reaction solution in the basic range.Alternatively, compound (I[) After adding and dissolving, compound (I
[) may be added, and if necessary, a base may be added to maintain the OpH value of the reaction solution in the basic range. In this case, the compound (][) may be used after being dissolved in the above-described solvent that does not mix uniformly with water.

The reaction temperature ranges from about 0 to 50°C, which poses no practical problem, but about 5 to 15°C is appropriate.

The reaction is completed in about 30 minutes to 6 hours. The completion can be confirmed by high performance liquid chromatography, thin layer chromatography, etc.

After the reaction is completed, p)1g of the reaction solution is adjusted to 12 to 13.5, and the aqueous layer is separated to remove unreacted compound (I[) and byproducts.

Compound (1) thus obtained can be purified by isolation and purification means known per se, such as concentration, vacuum concentration, vacuum distillation, liquid conversion, dissolution, solvent extraction, crystallization, recrystallization, chromatography, etc. Can be isolated and purified.

The raw material compounds (II) and (N) used in the present invention can be obtained by methods known per se, for example, JP-A-55-83796, JP-A-Sho.
5-130991, USF4163052, etc.

Next, the present invention will be explained in further detail by showing examples.

Example 1 Preparation of O-CI-(4-chlorophenyA/)-4-pyrazolyl] 0-ethyl-8-n-propylphosphorothioate 1-(4-chlorophenyA/)-4-hydroxybilacy/L/15 .02g (0,075 mo/I/) of water 24
．． 51 and then add 2.259 (0,
Add 0563 mo IV) and stir (it will dissolve and become a homogeneous solution). Add toluene 5.6.8m+/ to this and get intense L<
ffi While stirring, 30.89 g of a toluene solution containing 15.35 f (0.0757 mol) of o-ethyl-8-n-propyl-phosphorochloride is added dropwise over 2.5 hours. During this time, the reaction temperature was maintained at 15° C., and 1096 caustic soda water was added to keep the pH value of the reaction solution at 10.5. After completion of the dropwise addition, the reaction temperature was raised to 25 tE and stirred at the same temperature for 2 hours. The mixture was then cooled to 5°C, adjusted to pH 13.5 with a 28% aqueous sodium hydroxide solution, stirred for 30 minutes, and then separated. The toluene layer is further washed with 40 tsl of water and separated. The resulting toluene solution is concentrated under reduced pressure to obtain the title compound.

Yield: 279g Purity: 96.4% (HPLC (High Performance Liquid Chromatography; Cafum 10D8 (C-18) 4φ×25CIl,
Measured at temperature 40°C, mobile phase acetonitrile/water) Converted yield 26.94 (converted yield 99.5%) Comparative experiment 0-Cx-(4-chlorophenylene/l/)-4-pyrazolip) 0 -Production of ethyl-8-n-propyl phosphorothioate (method described in JP-A-55-130991) 1-(4-chloropheny A/)-, a-pyrazole 15
．． 029 (0,075 mo/L/) was dissolved in acetone Boat, anhydrous sodium carbonate 12, Og and 〇-ethyl/
l/5-n-propyl phosphorochloride 15.35f
(0,0757 mofi/) and heated under reflux for 2.5 hours. After the reaction is complete, acetone is distilled off, and toluene is added to the residue to make a toluene solution, which is then washed with water and dried over anhydrous sodium sulfate. When toluene is distilled off, 0-(1-
(4-chlorophenyfi/)-4-pyrazoli! ] 0-
Ethyl N-8-n-propyl phosphorothioate is obtained.

Yield: 22.771F Purity: 93.9% (measured by IPLC (high performance liquid chromatography) as in Example 1) Converted yield: 21
38f (yield: 7 & 151) Example 2 An organic phosphate derivative obtained in the same manner as in Example 1 is listed below.

(1) 0.0-diethyμ-〇-(2-isopropyl-4
-Methylpyrimidine-6-iμ) Phosphorothioate dark brown liquid hp 83-b (2) 0.0-dimethy1v-0-(4-methylthio-m
-) C/L/) yk Nupho p thioate colorless liquid slope p, 87℃ 10.01-■, d 1.569B (3
)O-(3,5,6-)dichloro-2-viridi/l/)
-0,0-dimethymu honuho pthioate white crystal UP, 45.5-46.51 m (4) 0.0-diethyl-〇-(2,3-dihydro-3
-Oxo-2-phenyl-6-pyridazinyl) phosphorothioate white crystals m, p, 54.5-56.0°C (5) (4-methylthiophenyl-fi/) di-n-propyμ phosphate pale yellow liquid, I ), 176℃/0.85 mmHg15-

Claims (1)

[Scope of Claims] A compound represented by the general formula [wherein R1 represents a lower alkoxy group, R2 represents a lower alkoxy group or lower alkylthio group, or an oxygen atom or a sulfur atom, and Y represents a halogen atom] A compound represented by the general formula [wherein R3 represents an optionally substituted phenyl group or an optionally substituted heterocyclic group] in water and a solvent that is not uniformly mixed with water under basic conditions. A method for producing a compound represented by the general formula [wherein R1, R2, R3 and X have the same meanings as above], characterized by reacting with: